Primary Literature Review
Association of the ADAM33 gene with asthma and bronchial hyper responsiveness.
The prevalence of asthma has increased significantly since the 1970s. As of 2009, asthma has been diagnosed in 300 million people worldwide and contributed to 250,000 deaths globally . Recent studies have shown that in addition to environmental exposures, a strong genetic component plays a part in development of asthmatic conditions . The biological pathways leading to asthma are influenced by multiple genes which additively contribute to asthmatic symptoms . The amount of genes contributing to asthmatic risk may exceed 100, but the individual effect of these genes may vary. Many genes have been associated with asthmatic conditions, but only ten genes have been independently verified in over ten independent studies . One of these genes was identified as ADAM33. This article explores the linkage between mutations in the gene region and the prevalence of asthmatic conditions.
To determine whether these polymorphisms in candidate genes were associated with asthma, association studies were performed. A genome-wide scan on 460 Caucasian families was performed to identify single nucleotide polymorphisms (SNPs) in unrelated effected offspring that were linked to asthmatic conditions or bronchial hyper responsiveness. An analysis was performed by looking at the differences in SNPs between individuals. SNPs occur when a single nucleotide in our DNA differs between separate individuals. Variations of these SNPs are an important part of how a person responds to pathogens, chemicals, drugs, allergens, or in protein functions. In this study, the authors are able to link SNPs found in ADAM33 to an increased prevalence of asthma. Twenty-four SNPs in three genes were found to be significant in either combined or separate US/UK analysis. A majority of SNPs (14) were in the ADAM33 gene. In general, the alleles in ADAM33 that increased susceptibility to asthma were common, with allele frequencies ranging from 20% to 95%.
The SNPs were further analyzed to determine if multiple SNPs were acting in combination to increase the risk of asthma. Haplotype pairs were constructed and the frequencies were compared between cases and controls. Haplotypes are combinations of DNA sequences that are transferred together in a chromosome. They are regions of DNA that are often passed on together across generations. By analyzing these regions the authors are able to determine which SNPs will most likely be passed on together. Eight haplotypes were determined to be highly significant at the P < .005 level, and six were considered significant at a P < .05 level.
Asthma is a complex disease, but learning more about how SNP mutations in ADAM33 give rise to asthmatic conditions will provide important clues in treating asthma. The ADAM33 gene has been found to be expressed in lung fibroblasts, and bronchial smooth muscle, but not in bronchial epithelial cells. The areas of expression along with the linkage analysis gives strong support for the association of ADAM33 in asthmatic conditions.
These results indicate a strong link between the ADAM33 gene and asthmatic conditions. This paper helps further the case for continuing ADAM33 research for treating asthmatic conditions. Further studies on the SNPs listed in this study may prove vital in understanding the role of ADAM33 in the pathogenesis of Asthma.
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